Pilot studies performed in this laboratory have documented the initial appearance of noradrenergic (NA) phenotypic characters in the autonomic nervous system of rat embryos (1-4). These studies have revealed two populations of NA cells: one in sympathetic gaglia expresses NA characteristics on gestational day 11.5 (ell.5) and subsequently maintains those traits; a second, located in embryonic gut mesenchyme, initially expresses NA traits on Ell.5, but loses those characteristics by E13.5. By comparing these two populations -- one in which NA characters are maintained, and one in which these same traits are lost -- we plan to identify some of the factors which control the maintenance (or loss) of neurotransmitter (NT) phenotypic expression during fetal development. We will focus on nerve growth factor (NGF) and glucocorticoid hormones, both known to affect NT development in general and NA development in particular. Specifically, the plan is to 1) determine the fate of the transiently NA gut cells by documenting the initial appearance in gut of other NTs known to be present in adult gut, and correlating their time of appearance with the disappearance of NA traits; 2) investigate further the effects of elevated maternal glucocorticoid hormones, known to delay the disappearance of NA traits in gut cells (84, 85); 3) investigate further the role of NGF in prolonging NA traits in gut cells (71); and 4) examine the possible role played by glucocorticoid hormones in mediating or facilitating the effect of NGF. A variety of histochemical techniques as well as radioimmunoassay, radiometric enzyme assay, and organotypic tissue culture will be brought to bear upon these issues.